Placental pathology in fetuses with and without congenital heart defects

Placental histopathologic evaluation of pregnancies affected by congenital heart defects (CHDs) can provide insight into the mechanism connecting placental and fetal vascular systems. The objective of this study was to evaluate the prevalence of maternal vascular malperfusion (MVM) and fetal vascular malperfusion (FVM) lesions of the placenta in pregnancies with and without fetal CHD on blinded pathologic examination.

This is a case-control study of pregnancies complicated by CHD at our institution from January 1, 2011 to June 25, 2021. Controls were matched to cases in a 2:1 ratio based on maternal age and gestational age at delivery. Placental and umbilical cord pathology slides were deidentified prior to standardized pathologic examination. There were two primary composite outcomes: MVM and FVM. The MVM composite included infarction and villous and vascular lesions. The FVM composite included thrombosis, villous lesions, and cord abnormalities. Primary composite outcomes were evaluated based on the presence or absence of a fetal CHD using t-tests and chi-squared or Fisher's exact tests, and a multivariable, conditional logistic regression model controlling for relevant confounding variables. Subgroup analysis was performed for those with and without maternal cardiovascular risk factors in the CHD group and for primary outcomes by cardiac lesion type.

A total of 351 patients were included: 117 cases and 234 controls. The CHD cohort had higher rates of neonatal intensive care unit (NICU) admission (91.5% vs. 22.2%, p < 0.001), neonatal death (12.8% vs. 0%, p < 0.001), and placental chorangiosis (12.0% vs. 4.7%, p = 0.01). Pregnancies with CHD were also more likely to have the FVM composite outcome (odds ratio [OR], 1.88; confidence interval [CI], 1.20-2.97), specifically villous lesions (26.5% vs. 10.7%, p = 0.0001), avascular villi (22.2% vs. 9.8%, p = 0.002), and a two-vessel umbilical cord (6.8% vs. 0.9%, p = 0.003). The MVM composite did not differ between groups. In the multivariable regression, the CHD group had higher odds of experiencing the FVM composite (OR, 2.01; CI, 1.14-3.56). Within the CHD cohort, those with hypertensive disorders of pregnancy were associated with the MVM composite outcome (53.9% vs. 36.2%, p = 0.05).

On blinded pathology review, those with fetal CHD were more likely to have FVM lesions. MVM lesions did not show an association with CHD in our cohort.